促血管生成素表达与人脑胶质瘤血管生成的关系研究

目的:研究促血管生成素(angiopoie-tins,Angs)蛋白表达水平与血管内皮生长因子(vascular endothelial growth factar,VEGF)和肿瘤内微血管密度(microvascular density,MVD)的关系,探讨其在人脑胶质瘤血管生成中的作用。方法:采用免疫组化方法检测42例人脑胶质瘤组织中Ang-1、Ang-2和VEGF的蛋白表达水平,并以抗CD34单克隆抗体显示血管内皮细胞,根据CD34阳性的血管计数来判定MVD。结果:42例人脑胶质瘤中,Ang-1+肿瘤的MVD比Ang-1-肿瘤高,但两者差异无统计学意义,P=0·156;Ang-2-和Ang-2+平均MVD分别是27·67和49·63,Ang-2+肿瘤MVD显著高于Ang-2-肿瘤,P=0·000。VEGF阳性表达时,Ang-2+肿瘤平均MVD显著高于Ang-2-肿瘤,分别为56·00和36·75,P=0·001;而VEGF阴性组中,Ang-2+肿瘤平均MVD与Ang-2-肿瘤几乎相等,分别为53·17和47·36,P=0·109。随胶质瘤恶性程度增加,Ang-1和Ang-2阳性表达率均升高,但Ang-2升高更明显,不同级别间Ang-2表达水平差异有统计学意义。结论:Ang-2高表达与人脑胶质瘤血管新生密切相关,Ang-2可以作为评价胶质瘤血管生成及恶性程度的一个重要指标。VEGF存在时,Ang-2过表达可促使肿瘤血管生成。肿瘤防治杂志,2005,12(19):1472-1475     

促血管生成素及其受体的异常表达与胃癌血管生成的关系

Objective： To explore angiopoietins （Ang-1, Ang-2）/Tie-2 expression and angiogenesis in stomach carcinomas. Methods： RT-PCR and immunohistochemistry were used to detect angiopoietins/Tie- 2 mRNA and protein expression in stomach carcinomas and their adjacent normal mucosa. Microvessel density （MVD） was counted according to CD34 immunohistochemical staining. Results： There was positive expression of Angiopoietins/Tie-2 mRNA and protein in stomach carcinomas and their paired adjacent normal mucosa. It was found that correlation between Ang-1 protein, Tie-2 mRNA expression and MVD was negative （F=-0.440, F=-0.267; P〈0.05）, while the correlation between Ang-2 mRNA and its protein, Ang-2/Ang-1 protein ratio and MVD was positive （F=0.319, F=-729, F=739; P〈0.05）. Moreover, MVD in groups with Ang-2 mRNAT/N ratio over 1.2 （the ratio of Ang-2 mRNA in stomach carcinoma to its adjacent normal mucosa） was higher than those with the ratio under 1.2. Conclusion： It was suggested that Ang-1 and Ang-2 antagonizes in the angiogenesis and the anglogenesis in tumor ultimately depended on Ang-2/Ang-1 ratio, once the expression of Ang-2 is higher than Ang-1 in some degree, the angiogenesis in tumors was promoted, otherwise oppositely. In other words, Ang-2 plays dominant role in the action of angiogenesis in tumors.     

Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density

Stromal cells, within and around the tumor, as well as tumor cells are both involved in angiogenesis which is an important step in tumor growth and metastasis. Among such stromal cells, macrophages are known to play various roles in tumor angiogenesis and have thus been called tumor-associated macrophages (TAMs). The TAM density, vascular endothelial growth factor (VEGF) expression and the microvessel density (MVD) were immunohistochemically evaluated in 249 paraffin-embedded sections of invasive ductal carcinoma of the breast. The TAM density and MVD were assessed as the average density of three hot spots at a magnification of x400 and x200, respectively. The TAM density showed a significant correlation with both the VEGF expression and MVD, while a significant correlation was also found between the VEGF expression and MVD. The TAM density was also associated with the nuclear grade, estrogen receptor status and MIB-1 count. Patients with a high TAM density had a significantly (p=0.0025) worse disease-free survival (DFS) prognosis than those with a low TAM density, while univariate analyses also indicated both the MVD (p<0.0001) and VEGF expression (p=0.0152) to be prognostic factors for DFS. A multivariate analysis indicated MVD (p=0.0057), as well as lymph node metastasis and the MIB-1 count, to be independently significant prognostic factors for DFS. In conclusion, the present study demonstrated a close association between TAM infiltration and both the VEGF expression and MVD. The prognostic significance of MVD was the strongest among these three factors in breast cancer. These findings suggested that the prognostic implications of TAM infiltration are due to the involvement of TAMs in tumor angiogenesis.     

The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus

The objective of this study was to investigate the expressions of angiogenic factors and elucidate their angiogenic and prognostic roles in hepatocellular carcinoma (HCC) with background of hepatitis B virus (HBV). We evaluated microvessel density (MVD) of HCC, and investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and matrix metalloproteinases-9 (MMP-9) in 67 specimens of surgically resected HCC, which were all positive for hepatitis B surface antigen. We investigated the relationship between their expressions and clinicopathological factors or prognosis. The microvessel density (MVD) of tumor tissue and surrounding normal liver tissue was 93.1 ± 43.8/mm² and 30.4 ± 14.8/mm², respectively. The MVD of well-differentiated HCC was significantly less than that of poorly differentiated HCC. MVD was positively correlated with VEGF and Ang-2 expression (P = 0.0023 and 0.0265, respectively). There was less tumor recurrence in low Ang-2 and low MMP-9 group than high Ang-2 and/or high MMP-9 group (P = 0.002). In Cox regression model, portal vein thrombus and intrahepatic metastasis was the risk factors of tumor recurrence (P = 0.003 and 0.001, respectively). Our study showed that the expression of VEGF and Ang-2 were positively correlated with MVD. Ang-2 expression and/or MMP-9 expression might be a significant predictive factor for recurrence after resection in HCC patients with the background of HBV.     

Angiogenesis in cholangiocellular carcinoma: expression of vascular endothelial growth factor, angiopoietin-1/2, thrombospondin-1 and clinicopathological significance

Angiogenesis in cholangiocellular carcinoma (CCC) has rarely been investigated. The aim of this study was to determine the angiogenesis status of CCC and assess its relationship with angiogenic factors and clinicopathological characteristics. We examined 33 surgically resected CCC specimens. Tumor angiogenesis was assessed by microvessel density (MVD) using the anti-CD34 antibody, and the expression of VEGF, Ang-1, Ang-2, and TSP-1 was determined by immunohistochemistry. The mean (+/- SD) MVD was 87.2+/-52.6/mm2 (range, 0-229/mm2). A total of 75.6% cases were positive for VEGF expression, 36% for Ang-1, 57.6% for Ang-2 and 45.5% for TSP-1. VEGF and Ang-2 expression was associated with a significantly higher level of MVD (p=0.004 and 0.015, respectively). TSP-1 expression was associated with a significantly lower level of MVD (p=0.005) and a higher level of intrahepatic metastasis (46.7% vs. 5.6%, p=0.012). There was no significant correlation between VEGF, Ang-1, Ang-2, and TSP-1 expression and tumor size, capsule formation, infiltration of capsule, portal vein invasion, intrahepatic metastasis or CCC differentiation. There was no significant correlation between MVD levels, VEGF, Ang-1, Ang-2, and TSP-1 expression and postoperative survival. A considerable degree of angiogenesis, comparable to that of other solid tumors, was observed in CCC. VEGF and Ang-2 might play a proangiogenic role, and TSP-1 may play an inhibitory role in CCC. Although TSP-1 may increase intrahepatic CCC metastases, neither MVD levels nor the expression of VEGF, Ang-1, or Ang-2 was associated with clinicopathological factors and prognosis.     

Significance of microvascular density and vascular endothelial growth factor in breast cancer

OBJECTIVE: To study the significance of vascular endothelial growth factor (VEGF) and microvascular density (MVD) expression in breast cancer. METHODS: The expression of MVD and VEGF was studied in 81 patients with primary breast cancer by SP immunohistochemical technique. RESULTS: There were 49 patients with high VEGF expression (60.5%) and 35 patients with high MVD expression (43.2%). There was significant correlation between VEGF or MVD expression and TNM stage, but not age, tumor size, ER expression or lymph node status. VEGF was significantly related with MVD expression. Univariate analysis showed that patients with low expression of VEGF and MVD had longer disease free survival (DFS) and overall survival (OS). Grouping univariate analysis showed that VEGF had significant correlation with the DFS of all grouped patients and the OS of patients with LN(+) or stage III lesions. MVD had significant correlation with the DFS and OS of LN(+) patients and the DFS of stage III lesion patients. Multivariate analysis showed that MVD was a risk predictor because of its positive statistic value, the higher expression, the shorter survival time of the patients. CONCLUSION: Both VEGF and MVD are useful prognostic factors in breast cancer. MVD appears to be a strong and independent biologic marker for breast cancer prognosis.     

Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma

Angiopoietin (Ang)-2 and vascular endothelial growth factor (VEGF) are thought to be critical regulators in tumor angiogenesis. We investigated the clinical significance of Ang-2 expression at the deepest invasive tumor site under the influence of VEGF expression in relation to angiogenesis, invasive/metastatic potential, and prognosis of advanced colorectal carcinoma (CRC). One hundred and fifty-two patients who underwent surgical resection for advanced CRC were enrolled in this study. Ang-2 and VEGF expression were examined immunohistochemically. Tumor microvessel density (MVD) was examined by immunohistochemical staining against CD34. Ang-2 and VEGF were expressed at the deepest invasive tumor site in 90 (59.2%) and 64 (42.1%) of 152 lesions, respectively. Patients with Ang-2 expression at the deepest invasive tumor site showed significantly (p<0.01) more frequent poorly histologic grade (71.9%), lymphatic involvement (65.9%), venous involvement (69.1%), lymph node metastasis (75.0%), liver metastasis (80.0%) and advanced disease (Dukes' stage C, 70.2%; stage D, 80.0%) than patients without Ang-2 expression. MVD was not significantly up-regulated by Ang-2 expression alone at the deepest invasive tumor site but was significantly up-regulated by VEGF expression at the deepest invasive tumor site under the positive-Ang-2 condition. In patients treated by curative surgery, patients with tumors showing both positive-Ang-2 and positive-VEGF condition at the deepest invasive tumor site had significantly poorer prognoses than patients with tumors under other conditions. Multivariate analysis with logistic regression for 5-year survival in cases of curative surgery showed that lymph node metastasis, VEGF expression and Ang-2 expression were significant factors to predict poor prognosis. Our results suggest that Ang-2 expression in collaboration with VEGF expression at the deepest invasive tumor site may result in tumor angiogenesis and that these angiogenic factors at the deepest invasive tumor site may be correlated with invasive/malignant potential and prognosis of advanced CRC.     

Evaluation of the Prognostic Role of Vascular Endothelial Growth Factor and Microvessel Density in Stages I and II Breast Cancer Patients

In this study, we retrospectively evaluated the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in 228 and 213 specimens, respectively, from stages I and II breast cancer patients (pts) enrolled in a randomized phase III adjuvant chemotherapy trial comparing epirubicin to CMF, while tamoxifen was given to all postmenopausal pts. The expression of VEGF and MVD was assessed on tissue sections formalin-fixed and paraffin-embedded by immunohistochemical staining using anti-VEGF antibody of human origin and anti-CD34 monoclonal antibody. Univariate and multivariate analysis were performed using chi squared test, log-rank test and Cox's regression model. Sixty four of 228 pts were classified as VEGF positive (28%) with no significant difference in the two treatment arms. In 213 pts evaluated for CD34, 103 pts (48%) were classified as MVD high. No significant association between VEGF and MVD was found, and neither were they correlated with many known prognostic factors such as age, tumor size, nodal status, and histological grade. The only significant correlations observed were between VEGF and estrogen receptor (ER) status (p = 0.013) and between MVD and HER2 overexpression (p = 0.023). At a median follow up of 96 months VEGF and MVD were not correlated with relapse-free survival (RFS) and overall survival (OS) in all pts and in pts assigned to one of the two treatment arms. In conclusion, VEGF and MVD retrospectively evaluated, cannot be considered prognostic factors in node negative (N–) high risk and node positive (N+) breast cancer pts treated with two different regimens of adjuvant chemotherapy.     

非小细胞肺癌患者血清中VEGF和Ang-2的表达和临床意义

目的:检测非小细胞肺癌（NSCLC）患者血清中血管内皮生长因子（VEGF）和血管生成素-2（Ang-2）的含量,探讨血清中VEGF和Ang-2与肿瘤血管生成的关系及其临床意义。方法:收集40例NSCLC患者血清和肿瘤组织,以40例健康志愿者血清为对照,采用ELISA方法检测血清中VEGF和Ang-2的含量,应用免疫组化法检测肿瘤组织中的微血管密度（MVD）,分析血清中VEGF和Ang-2与肿瘤血管生成、临床病理资料和预后的相关性。结果:NSCLC患者血清中VEGF［（625.6±312.5）pg/ml］和Ang-2［（2450.2±1021.1）pg/ml］的含量明显高于正常对照组血清中VEGF［（321.4±102.6）pg/ml］和Ang-2［（1020.6±421.6）pg/ml］的含量（P<0.05）。NSCLC患者血清中VEGF和Ang-2的含量均与肿瘤的MVD呈正相关(r=0．525,P<0.01;r=0．612,P<0.01)。NSCLC患者血清中VEGF和Ang-2的含量与肿瘤大小、淋巴结转移及临床分期有关（P<0.05）。血清中VEGF和Ang-2高表达的患者总生存时间明显低于低表达患者（P<0.05）。结论:VEGF和Ang-2 在NSCLC的血管生成和发展中发挥重要作用,两者可作为NSCLC诊断和预后判断的潜在的分子标志物。     

促血管生成素-2对胃癌血管生成的双向效应

目的　探讨促血管生成素 2 (Ang 2 )在胃癌血管生成中的作用。方法　运用RT PCR和S P免疫组化方法检测Ang 2mRNA、血管内皮生长因子 (VEGF)、CD34蛋白在 36例胃癌及其相应癌旁胃黏膜组织中的表达。结果　胃癌组织及其相应癌旁胃黏膜组织均见有Ang 2mRNA阳性表达 ,胃癌组织Ang 2mRNA的总体表达水平与微血管密度 (MVD)未见明显相关。胃癌组织Ang 2mRNA表达水平低于癌旁胃黏膜组织者 2 7例 ,其癌组织中 ,Ang 2mRNA的表达水平与MVD呈正相关 (r=0 .4 11,P <0 .0 5 ) ;同时 ,VEGF阳性表达者的MVD(45 .4 5± 10 .30 )明显高于VEGF阴性染色者 (30 .15± 8.6 9,P <0 .0 5 ) ,即在Ang 2表达上调的情况下VEGF促进血管生成。胃癌组织Ang 2mRNA表达水平高于癌旁组织者 9例 ,其癌组织中Ang 2mRNA的表达水平与肿瘤组织的MVD呈负相关 (r =- 0 .75 8,P <0 .0 5 ) ,VEGF的阳性表达者与阴性染色者间 ,MVD差异无显著性 ,即Ang 2抑制血管生成与VEGF的表达无相关性。结论　Ang 2对胃癌血管生成具有双向调节作用。     

胃癌组织中Ａｎｇ ２和ＶＥＧＦ的表达与血管生成的关系

目的：研究胃癌组织中血管生成素-２（Ａｎｇ-２）和血管内皮生长因子（ＶＥＧＦ）的表达与临床病理学特征和肿瘤血管生成的关系。方法：应用免疫组织化学方法检测５５例胃癌组织以及１２例胃癌癌旁组织和正常胃组织中Ａｎｇ-２、ＶＥＧＦ表达及微血管密度（ＭＶＤ）。结果：Ａｎｇ-２、ＶＥＧＦ表达及ＭＶＤ在胃癌组织中均显著高于癌旁组织及正常胃组织（Ｐ＜０.０５）;胃癌组织Ａｎｇ-２、ＶＥＧＦ表达与浸润深度、淋巴结转移、病理分期、肿瘤分化程度密切相关（Ｐ＜０.０５）;Ａｎｇ-２与ＶＥＧＦ表达呈正相关性（Ｐ＜０.０５）。结论：Ａｎｇ-２、ＶＥＧＦ在胃癌组织中高表达,两者在胃癌的肿瘤血管生成和进展中起重要作用。     

Tumor angiogenesis in breast cancer: Its importance as a prognostic indicator and the association with vascular endothelial growth factor expression

Summary The importance of tumor angiogenesis in the process of tumor growth and progression in solid tumors has been widely accepted. We have investigated the significance of tumor angiogenesis as a prognostic indicator in a retrospective study including 328 primary breast cancer patients. The postoperative survey demonstrated that the microvessel density (MVD) evaluated by immunocytochemical staining for factor VIII-related antigen is a potent prognostic indicator. The relapse-free survival (RFS) rate of patients with over 100 microvessels/mm² in a microscopic field was significantly worse compared to that of patients with less than 100 microvessels/mm² (p<0.00001). The significance of MVD was found in both node-negative and node-positve patients (p< 0.005 and p<0.01, respectively). Multivariate analysis confirmed that MVD is an independent prognostic indicator for RFS. In the background factor analysis, MVD was significantly correlated with the number of metastatic nodes (p<0.01). In addition, the immunocytochemical analysis for vascular endothelial growth factor (VEGF) demonstrated a close association between the increase in MVD and the expression of VEGF (p<0.001). VEGF status also was a significant prognostic indicator in univariate analysis for RFS (p<0.01). It was concluded that MVD is a potent prognostic indicator in primary breast cancer. Furthermore, it was also suggested that VEGF plays crucial roles in the promotion of angiogenesis in breast cancer.Abbreviations MVD microvessel density - VEGF vascular endothelial growth factor     

Vascular Endothelial Growth Factor Expression in Invasive Ductal Carcinoma of Breast

Objective： To detect the expression of VEGF and MVD count in invasive ductal carcinoma of breast to clarify the association of VEGF expression and MVD count with the clinicopathologic features. Methods： The expressions of VEGF, ER, PR, C-erbB-2 and MVD count in 88 cases of invasive ductal carcinoma of breast were examined by immunohistochemistry staining （SP-method）. Results： Sixty-two out of the eighty-eight specimens of breast carcinoma （70.45%） showed positive expression of VEGF. The positive rate of VEGF in cases with lymph node metastasis was higher than that without lymph node metastasis （P〈0.05）. The positive rate of VEGF in stage IIb-Ⅲ was higher than that in stage Ⅰ-Ⅱa （P〈0.05）. The positive rate of VEGF in C-erbB-2 positive group was higher than that in C-erbB-2 negative group （P〈0.05）. Higher expression of VEGF was observed in cases with higher tissue differentiation degree （P〈0.05）. Also, significant higher MVD count was observed in cases with higher tissue differentiation degree （P〈0.01）. The MVD count increased significantly with the increase of the expression of VEGF （P〈0.01）. Conclusion： The result of this study suggested that in invasive ductal carcinoma of breast, angiogenesis and metastasis were mediated mainly by VEGF. The expression of VEGF and MVD might be reference predictors for the biological behavior of breast carcinoma. The antiangiogenic therapy which used VEGF as a target would become a new method to treat patients who were C-erbB-2 positive in the future.     

血管生成素-2及其受体在卵巢癌组织中的表达及与血管生成的关系

目的探讨血管生成素-2（Ang-2）及其受体（Tie-2）在卵巢癌中的表达及与血管生成、临床病理特征的关系。方法采用RT-PCR法检测25例正常卵巢组织标本、25例良性卵巢肿瘤和65例恶性卵巢肿瘤中Ang-2及其受体Tie-2的表达水平,并采用免疫组织化学法检测各标本的微血管密度（MVD）。结果恶性组MVD显著高于良性组（t=2.61,P<0.05）,不同临床分期的卵巢癌MVD的差异有统计学意义（F=4.618,P<0.05）。恶性组Ang-2 mRNA阳性率和表达水平显著高于良性组和对照组（P<0.05）,不同临床分期的卵巢癌标本Ang-2 mRNA表达水平有显著性差异（0.298±0.022 vs.0.206±0086,P<0.05）。恶性组MVD与其Ang-2 mRNA表达水平呈正相关关系（rMV=0.685,P<0.05）。仅在5例恶性卵巢癌标本中检测到 Tie-2 mRNA表达,良性组和对照组未检出。结论恶性卵巢癌组织中高表达Ang-2,其与卵巢癌肿瘤血管大量形成有关。     

三阴性乳腺癌组织Angs/Tie-2和VEGF的表达及其意义的探讨

目的:研究Ang-1、Ang-2和Tie-2及VEGF蛋白在三阴性乳腺癌(TNBC)组织中的表达及其与MVD的关系,并分析其与TNBC临床病理学特征及其预后的关系。方法:应用免疫组化SP法对45例TNBC组织中Ang-1、Ang-2和Tie-2及VEGF蛋白表达进行检测,并用同样方法检测45例TNBC组织中CD34的表达以评估MVD。结果:TNBC肿瘤组织中Ang-1、Ang-2和Tie-2及VEGF蛋白表达率分别为31.1%(14/45)、57.8%(26/45)、44.4%(20/45)和66.7%(30/45)。Ang-2蛋白表达与Tie-2蛋白表达呈正相关(r=0.312,P=0.037),Ang-2蛋白表达与VEGF蛋白表达呈正相关(r=0.350,P=0.018)。MVD在Ang-2蛋白阳性表达组显著高于阴性表达组(t=-9.110,P=0.000);MVD在VEGF蛋白阳性表达组显著高于阴性表达组(t=-0.889,P=0.000)。Ang-1、Ang-2、和Tie-2及VEGF蛋白表达与年龄、绝经状态、病理分期、肿瘤大小、淋巴结转移均无相关性(P均>0.05)。TNBC术后生存时间与Ang-1...     

促血管生成素及其受体的异常表达与胃癌血管生成的关系

目的探讨促血管生成素（Ang）及其受体Tie-2在胃癌中的表达及其与胃癌血管生成的关系。方法应用RT—PCR和免疫组化分析技术,检测68例胃癌组织及其相应的癌旁胃黏膜Ang-1、Ang-2及Tie-2 mRNA和蛋白表达水平,计数微血管密度（MVD）。结果胃癌组织及相应癌旁组织均见Ang—1、Ang-2及Tie-2 mRNA的表达,Ang-1蛋白、Tie-2 mRNA表达水平与MVD呈负相关（r=-0．440,r=-0．267;P〈O．05）,Ang-2 mRNA及蛋白表达水平与MVD呈正相关（r=0．319,r=0．729;P〈0．05）,Ang-2／Ang-1蛋白表达的比值与MVD呈正相关（r=0．739,P〈0．05）。在Ang-2 mRNAT／N比值（胃癌与癌旁胃粘膜mRNA表达水平的比值）〉1．2时,其MVD均高于T／N比值〈1．2者,而与Ang—1 mRNA的表达情况无关。结论Ang—1与Ang-2蛋白在胃癌血管生成中相互拮抗,Ang-2／Ang—1的比值可能是决定胃癌血管生成和肿瘤生长的最终因素。当Ang-2高表达而Ang-1低表达时,促进胃癌的血管生成;反之,则抑制胃癌血管生成。推测Angs及其受体系统在胃癌血管生成中的调节作用是以Ang-2的作用为主导的。     

血管内皮生长因子、血管生成素在食管鳞状细胞癌组织中的表达及其意义

目的 研究血管内皮生长因子(VEGF)、血管生成素(Ang)-1及Ang-2在食管鳞状细胞癌(ESCC)中的表达及其与预后的关系.方法 用免疫组织化学二步法检测60份ESCC、20份食管癌旁组织及10份正常食管黏膜上皮组织中VEGF、Ang-1及Ang-2的表达,计数微血管密度(MVD).结果 ESCC与食管癌旁组织及食管正常鳞状上皮组织比较,Ang-1表达率显著降低,而VEGF及Ang-2表达率则显著升高(P＜0.05).MVD在Ang-1阴性表达组显著高于阳性表达组(P=0.000);MVD在VEGF、Ang-2阳性表达组显著高于阴性表达组(P＜0.05).Ang-1表达与肿瘤分化程度显著相关(P=0.013).T3、T4期VEGF和Ang-2表达率显著高于T1、T2期(P＜0.05);VEGF及Ang-2在有淋巴结转移者显著高于无淋巴结转移者(P＜0.001).VEGF及Ang-2表达阳性组术后3年生存率低于阴性表达组(P＜0.05),Ang-1表达阳性和阴性组比较,差异无统计学意义(P=0.749).结论 Ang-1表达的降低及Ang-2、VEGF表达的增高可能与食管癌的发生、发展密切相关;VEGF及Ang-2在食管癌中表达提示预后不良.     

Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose–dense sequential adjuvant chemotherapy

Summary Purpose To assess the prognostic and predictive significance of HER-2 overexpression and high expression of VEGF in high-risk patients with breast cancer treated with dose–dense sequential chemotherapy. Patients and methods From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m² followed by three cycles of paclitaxel (T) 250 mg/m² followed by three cycles of “intensified” CMF (cyclophosphamide 840 mg/m², methotrexate 47 mg/m² and fluorouracil 840 mg/m²) or to four cycles of E, followed by four cycles of CMF. HER-2 was assessed by immunohistochemistry (IHC) in 394 patients, and by fluorescence in situ hybridization (FISH) in cases scored as 2+ by IHC. VEGF was evaluated in 323 patients by IHC. Results HER-2 overexpression was detected in 123 patients (31%) and high expression of VEGF in 233 (72%). The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining (35% vs. 21%, p=0.02). Overexpression of HER-2 was significantly associated with negative hormonal status, high histologic grade and larger tumors. HER-2 overexpression was a significant negative predictor of DFS (p=0.002), but not of OS. Adjusting for HER-2 overexpression, DFS and OS did not significantly differ between treatment groups. Positive VEGF staining was not associated with receptor status, number of positive nodes, grade, tumor size, incidence of relapse or death. Conclusions For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident.     

Angiopoietin-2和VEGF在口腔鳞癌中的表达及意义

目的研究口腔鳞癌组织中Ang-2和VEGF的表达并分析它们与肿瘤临床病理学特征和血管生成及血管成熟间的关系。方法:用常规的免疫组织化学的方法检测41例口腔鳞癌及30例癌旁正常组织和10例正常口腔黏膜中的Ang-2及VEGF的表达;通过双标免疫组织化学法同时染CD34(标记所有血管内皮细胞)和α-平滑肌肌动蛋白(标记血管壁细胞包括血管平滑肌细胞和周细胞)评估微血管密度(MVD)及血管成熟指数(VMI)。结果在口腔鳞癌组织中Ang-2和VEGF的阳性表达率分别为21(51.22%)和26(63.42%);Ang-2和VEGF在口腔鳞癌组织中表达显著高于它们在癌旁正常组织(P<0.05)和正常口腔黏膜组织中的表达(P<0.05);Ang-2表达与肿瘤的淋巴结转移密切相关(P<0.01)而VEGF表达与肿瘤的肿瘤分化程度相关(P<0.05),它们与病人的性别、年龄及TNM分期无关(P>0.05);Ang-2和VEGF表达阳性的鳞癌组织MVD显著高于它们阴性表达组(P<0.05)而Ang-2表达阳性的鳞癌组织VMI显著低于Ang-2表达阴性组(P<0.05)。在联合VEGF表达的情况下,同时表达Ang-2和VEGF的肿瘤MVD(51.08±2.99)显著高于其他任何表达状况(P<0.05)。结论Ang-2和VEGF在口腔鳞癌组织中的过表达可能在口腔鳞癌的进展过程中起重要作用;它们与肿瘤的血管生成和成熟密切有关。